CN101575309B - Method for synthesizing (S)-oxiracetam - Google Patents
Method for synthesizing (S)-oxiracetam Download PDFInfo
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- CN101575309B CN101575309B CN2009100501165A CN200910050116A CN101575309B CN 101575309 B CN101575309 B CN 101575309B CN 2009100501165 A CN2009100501165 A CN 2009100501165A CN 200910050116 A CN200910050116 A CN 200910050116A CN 101575309 B CN101575309 B CN 101575309B
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Abstract
The invention discloses a method for synthesizing (S)-oxiracetam, which comprises the following steps: (1) using glycine as a starting material to react with a chiral reagent (S)-4-halogen-3-hydroxy butyrate so as to obtain an intermediate I; (2) performing esterification reaction on the intermediate I and ethanol to obtain an intermediate II; and (3) reacting the intermediate II with ammonia water for aminolysis to obtain the target product (S)-oxiracetam. The purity of the (S)-oxiracetam obtained by the method can reach over 98.5 percent, and the optical purity can reach over 98 percent. Compared with the prior art, the method for synthesizing the (S)-oxiracetam has the advantages of cheap and easily obtained raw materials, low cost and simple and convenient operation.
Description
Technical field
The present invention relates to a kind of method of synthetic (S)-oxiracetam.
Background technology
Oxiracetam be by Italian SmithKline than Qie Mu company in 1974 synthetic nootropics first, by two kinds of isomer (S)-oxiracetam ((S)-oxiracetam) and (R)-oxiracetam (raceme of (R)-oxiracetam) form.(S)-and oxiracetam is a single enantiomer of oxiracetam, chemistry is by name: (S)-4-hydroxyl-2 OXo-1-pyrrolidine ethanamide.The nootropics oxiracetam is a kind of synthetic hydroxy-amino-butyric acid (GABOB) derivative, and it is that a kind of can the promotion learnt, memory, the medicine for central nervous system of protection injured nerve cell.
At present, the method for synthetic (the S)-oxiracetam of bibliographical information has three kinds:
U.S. Pat 4173569 has been addressed a kind of synthetic method of (S)-oxiracetam: (S)-and GABOB is a starting raw material; through sillylation reagent protection hydroxyl; product after the cyclization and the reaction of halogenated acetic acids ethyl ester; reaction product is through the deprotection base; ammonia is separated, and obtains target compound at last.This kind preparation method is not suitable for commercial scale production, because it has a lot of shortcomings, can increase reactions steps as using protecting group that hydroxyl is protected, and wastes raw material, and is consuming time longer, increases cost, and total recovery is reduced.In addition, in this reaction process, need carry out column chromatography purification, just can carry out next step reaction intermediate.These shortcomings all are very disadvantageous for commercial scale production.
Document: Tetrahedron:Asymmetry 1992,3 (11) has reported a kind of method of synthetic this compound; With oxysuccinic acid and glycine methyl ester is starting raw material, and Acetyl Chloride 98Min. protection hydroxyl through selective reduction, removes hydroxyl, the deprotection base, and ammonia is separated, and obtains target compound.In this method, need carry out a selective reduction and cause and produce multiple by product, and each intermediate all needs column chromatography purification, just can carry out next step reaction.Such technology can not satisfy the requirement of industrially scalable equally.
The disclosed technology of patent WO2005/115978, wherein the reaction of (S)-4-chloro-ethyl 3-hydroxybutanoate and G-NH2 obtains target compound, perhaps with the glycine ethyl ester reaction, separates through ammonia and obtains target compound.Wherein (S)-4-chloro-3-butyric ester and sweet amine amide react under alkaline condition that to obtain the finished product oxiracetam be to add the alkalescence that alkali is controlled reaction solution by disposable, but, so directly influenced the purity and the yield of oxiracetam because oxiracetam is destroyed easily in strong base solution; Adopt silica gel column chromatography method in addition in purifying the finished product oxiracetam, the elutriant of use is organic mixed solvent, and quantity of solvent is big, be difficult for reclaiming, and the cost height, and silica gel column chromatography method also is not suitable for industrial amplification production.
Summary of the invention
The method that the purpose of this invention is to provide a kind of synthetic (S)-oxiracetam is to overcome the above-mentioned defective that prior art exists.
Method of the present invention comprises the steps:
(1) with the glycine is starting raw material,, obtains intermediate compound I with chiral reagent (S)-4-halogen-3-butyric ester reaction;
(2) intermediate compound I and ethanol are carried out esterification, obtain intermediate II;
(3) with intermediate II and ammoniacal liquor reaction, ammonia is separated, and obtains target product (S)-oxiracetam;
Concrete, comprise the steps:
(1) with glycine in water, pH is under 8～12 the condition, with (S)-4-halogen-3-butyric ester reaction, obtains the intermediate compound I aqueous solution;
Said (S)-4-halogen-3-butyric ester is the compound with following general structure:
Wherein: X represents Br, and Cl or I, R represent the alkyl of 1-2 carbon atom;
Preferably, (S)-4-halogen-3-butyric ester is (S)-4-chloro-3-beta-hydroxymethyl butyrate, (S)-4-chloro-ethyl 3-hydroxybutanoate, (S)-4-bromo-3-beta-hydroxymethyl butyrate, (S)-4-bromo-ethyl 3-hydroxybutanoate, (S)-4-iodo-3-beta-hydroxymethyl butyrate or (S)-4-iodo-ethyl 3-hydroxybutanoate;
Said (S)-4-halogen-3-butyric ester can adopt the commercially available prod;
The adjusting of pH can realize by adding alkaline matter, said alkaline matter is selected from the aqueous sodium hydroxide solution of 5M～10M or the potassium hydroxide aqueous solution of 5M～10M, temperature of reaction is 60～100 ℃, reaction times is 5～10 hours, glycine with (S)-mol ratio of 4-halogen-3-butyric ester is:
Glycine: (S)-4-halogen-3-butyric ester=1: 1～1.4;
Preferably, (S)-4-halogen-3-butyric ester with glycine and gross weight 25～35% reacted 1～3 hour earlier, and then (the S)-4-halogen-3-butyric ester that adds gross weight 25～35% reacted 1～3 hour, and then (the S)-4-halogen-3-butyric ester that adds surplus reacted 4～10 hours, acquisition contains the aqueous solution of intermediate compound I, collects intermediate compound I then from the aqueous solution that contains intermediate compound I;
Preferably, from the aqueous solution that contains intermediate compound I, collect the method for intermediate compound I, comprise the steps: with weight concentration to be that 35～37% hydrochloric acid is transferred pH value of solution value to 1, concentrated, obtain intermediate compound I;
(2) intermediate compound I that will obtain from step (1) with ethanol heating reflux reaction 5～10 hours in the presence of the catalyzer of catalytic amount, in the time of reaction, is told the water that reaction generates in solvent, collect the acquisition intermediate II then;
Said solvent there is no particular requirement, more than one in preferred hexanaphthene, benzene or the toluene;
Said catalyzer is selected from mineral acid or organic acid, and preferred mineral acid is sulfuric acid or phosphoric acid, and preferred organic acid is Phenylsulfonic acid or tosic acid etc.;
Intermediate compound I in the intermediate compound I aqueous solution and alcoholic acid mol ratio are:
Intermediate compound I in the intermediate compound I aqueous solution: ethanol=1: 18～20;
(3) intermediate II that step (2) is obtained was reacted 4～8 hours with ammoniacal liquor down at 20～30 ℃, collected target product (S)-oxiracetam then from reaction product;
In the ammonia in the ammoniacal liquor, intermediate II: the mol ratio of ammonia is:
Intermediate II: ammonia=1: 12～1 5;
The weight concentration of described ammoniacal liquor is 25～28%;
Preferably, collect the method for target product (S)-oxiracetam in the said reaction product, comprise the steps:
Reaction product is handled through strong acid cation exchange resin column, with the strongly basic anion exchange resin neutralization, filtered then, collect filtrate, reconcentration adds alcohol crystal then, obtains product (S)-oxiracetam.
The preferred 732# storng-acid cation exchange resin of described storng-acid cation exchange resin, the preferred 711# strong basicity of described strongly basic anion exchange resin Zeo-karb;
The consumption of strongly acidic cation exchange tree is:
Reaction product: storng-acid cation exchange resin=1 gram: 8～12 milliliters;
The consumption of strongly basic anion exchange resin is:
Reaction product: strongly basic anion exchange resin=1 gram: 4～8 milliliters;
Consumption of ethanol is:
Thick product: ethanol=1 gram: 1.0～3.0 milliliters;
Reaction expression is as follows:
Method of the present invention, the purity of (the S)-oxiracetam that is obtained can reach more than 98.5%, and optical purity can reach more than 98%.
Adopt synthetic (the S)-oxiracetam of the above-mentioned method of the present invention, compared with prior art, raw material is cheap and easy to get, and cost is lower, and is easy and simple to handle.
Embodiment
Embodiment 1
(1) preparation of intermediate compound I:
7.5g (100mmol) glycine is suspended in the 17ml water, be heated to 65 ℃, stirring makes the glycine dissolving, be added dropwise to the sodium hydroxide solution of 5M, the pH that makes reaction solution is 8, add 6.1g (36.6mmol) (S)-4-chloro-ethyl 3-hydroxybutanoate, the temperature of reaction temperature control reacted 1.5 hours at 70 ℃, add 6.1g (36.6mmol) (S)-4-chloro-ethyl 3-hydroxybutanoate, be added dropwise to 5M sodium hydroxide solution control pH simultaneously 8, reacted 1.5 hours, after the chloro thing of adding to be detected has reacted, add again 6.1g (36.6mmol) (S)-4-chloro-ethyl 3-hydroxybutanoate reaction 8 hours, after detection reaction finishes, get the aqueous solution of intermediate compound I.With weight concentration is that 35% hydrochloric acid is transferred pH value of solution value to 1, and concentrated aqueous solution obtains intermediate compound I 21.2g;
(2) preparation of intermediate II
Intermediate compound I, 140ml ethanol, the 2.6ml weight concentration that step (1) is obtained is that 98% sulfuric acid and 200ml hexanaphthene place the reaction flask that is provided with division box, stir down, heating reflux reaction 7 hours is chilled to room temperature, filters, clean filter cake with ethanol, divide water-yielding stratum in the filtrate, use chloroform extraction, colourless to organic layer, concentrate water layer, obtain the 11.3g intermediate II;
(3) (S)-preparation of oxiracetam:
Add the 45g weight concentration in the intermediate II that step (2) is obtained and be 25% ammoniacal liquor, 25 ℃ of stirring reactions 6 hours concentrate, obtain thick thing, thick liquid is dissolved in 15mL water, handles, merge collection and treatment liquid through the 120mL732# strong acid cation exchange resin column, neutralize with 60mL 711# strongly basic anion exchange resin, the filtering resin, filtrate concentrates, and obtains crude product 10.6g, crude product adopts ethyl alcohol recrystallization, gets product 4.9gS-oxiracetam.Chromatographic purity is 98.80%.
Embodiment 2
(1) preparation of intermediate compound I:
The 7.5g glycine is suspended in the 17ml water, be heated to 65 ℃, stirring makes the glycine dissolving, be added dropwise to the 5M sodium hydroxide solution, the pH that makes reaction solution is 9, add 9.9g (S)-4-bromo-ethyl 3-hydroxybutanoate, the temperature of reaction temperature control is at 70 ℃, stirring reaction 1.5 hours, add 9.9g (S)-4-bromo-ethyl 3-hydroxybutanoate, be added dropwise to 5M sodium hydroxide solution control pH 9, stirring reaction 1.5 hours is after the bromo-derivative of adding to be detected has reacted, add 9.9g (S)-4-bromo-ethyl 3-hydroxybutanoate again, reacted 8.5 hours, and after detection reaction finishes, got the aqueous solution of intermediate compound I.With weight concentration is that 35% hydrochloric acid is transferred pH value of solution value to 1, and concentrated aqueous solution obtains the 20.0g intermediate compound I.
(2) preparation of intermediate II
Intermediate compound I, 146ml ethanol with step (1) acquisition, 3.3ml weight concentration is 98% sulfuric acid and 200ml hexanaphthene, place the reaction flask that is provided with division box, reflux divides the water reaction after 7 hours under stirring, being chilled to room temperature filters, clean filter cake with ethanol, divide water-yielding stratum in the filtrate, concentrate the 11.0g intermediate II.
(3) (S)-preparation of oxiracetam:
Add the 60g weight concentration in the intermediate II that step (2) is obtained and be 25% ammoniacal liquor, 30 ℃ of stirring reactions 8 hours, concentrate, obtain thick thing, thick liquid is dissolved in 15mL water, handle through the 110mL732# strong acid cation exchange resin column, merge collection and treatment liquid, with the neutralization of 50mL 711# strongly basic anion exchange resin, behind the filtering resin, concentrate filter and obtain crude product 9.8g night, crude product adopts ethyl alcohol recrystallization to get product 3.9gS-oxiracetam.
Embodiment 3
(1) preparation of intermediate compound I:
7.5g (100mmol) glycine is suspended in the 17ml water, be heated to 60 ℃ of stirrings and make the glycine dissolving, be added dropwise to the 10M sodium hydroxide solution, the pH that makes reaction solution is 12, add 5.5g (36.6mmol) (S)-4-chloro-3-beta-hydroxymethyl butyrate, the temperature of reaction temperature control is at 100 ℃, stirring reaction 1.5 hours, add 5.5g (36.6mmol) (S)-4-chloro-3-beta-hydroxymethyl butyrate, be added dropwise to 10M sodium hydroxide solution control pH simultaneously 12, stirred 1.5 hours, after the chloro thing of adding to be detected has reacted, add again 5.5g (36.6mmol) (S)-4-chloro-3-beta-hydroxymethyl butyrate stirs, reacted 8 hours, after detection reaction finishes, get the aqueous solution of intermediate compound I.With weight concentration is that 35% hydrochloric acid is transferred pH value of solution value to 1, and concentrated aqueous solution obtains the 19.8g intermediate compound I.
(2) preparation of intermediate II
Intermediate compound I, 130ml ethanol, the 3.2ml weight concentration that step (1) is obtained is 98% sulfuric acid and 200ml hexanaphthene, place the reaction flask that is provided with division box, reflux divides the water reaction after 7 hours under stirring, being chilled to room temperature filters, clean filter cake with ethanol, divide water-yielding stratum in the filtrate, use chloroform extraction, colourless to organic layer, concentrated water layer gets the 10.5g crude product.
(3) (S)-preparation of oxiracetam:
Add the 42g weight concentration in the crude product that step (2) is obtained and be 25% ammoniacal liquor, 30 ℃ of stirring reactions 8 hours, concentrate, obtain thick thing, thick liquid is dissolved in 12mL water, handle through 90mL 732# strong acid cation exchange resin column, merge collection and treatment liquid, with the neutralization of 40mL 711# strongly basic anion exchange resin, behind the filtering resin, concentrate filter and obtain crude product 9.4g night, crude product adopts ethyl alcohol recrystallization to get product 4.0gS-oxiracetam.
Claims (9)
1. the method for synthetic (S)-oxiracetam is characterized in that, comprises the steps:
(1) with the glycine is starting raw material,, obtains intermediate compound I with chiral reagent (S)-4-halogen-3-butyric ester reaction;
(2) intermediate compound I and ethanol are carried out esterification, obtain intermediate II;
(3) with intermediate II and ammoniacal liquor reaction, ammonia is separated, and obtains target product (S)-oxiracetam;
Wherein, step (1) comprises the steps: glycine in water, and pH is that with (S)-4-halogen-3-butyric ester reaction, temperature of reaction is 60～100 ℃ under 8～12 the condition, and the reaction times is 5～10 hours.
2. method according to claim 1 is characterized in that, said (S)-4-halogen-3-butyric ester is the compound with following general structure:
Wherein: X represents Br, and Cl or I, R represent the alkyl of 1-2 carbon atom.
3. method according to claim 1, it is characterized in that described (S)-4-halogen-3-butyric ester is (S)-4-chloro-3-beta-hydroxymethyl butyrate, (S)-4-chloro-ethyl 3-hydroxybutanoate, (S)-4-bromo-3-beta-hydroxymethyl butyrate, (S)-4-bromo-ethyl 3-hydroxybutanoate, (S)-4-iodo-3-beta-hydroxymethyl butyrate or (S)-4-iodo-ethyl 3-hydroxybutanoate.
4. method according to claim 1, it is characterized in that, add alkaline matter and regulate pH, said alkaline matter is selected from the aqueous sodium hydroxide solution of 5M～10M or the potassium hydroxide aqueous solution of 5M～10M, glycine with (S)-mol ratio of 4-halogen-3-butyric ester is: glycine: (S)-4-halogen-3-butyric ester=1: 1～1.4.
5. method according to claim 4, it is characterized in that, (S)-4-halogen-3-butyric ester with glycine and gross weight 25～35% reacted 1～3 hour earlier, and then (the S)-4-halogen-3-butyric ester that adds gross weight 25～35% reacted 1～3 hour, and then (the S)-4-halogen-3-butyric ester that adds surplus reacted 4～10 hours, acquisition contains the aqueous solution of intermediate compound I, collects intermediate compound I then from the aqueous solution that contains intermediate compound I.
6. method according to claim 1, it is characterized in that, wherein, step (2) comprises the steps: the intermediate compound I from step (1) acquisition, in solvent with ethanol heating reflux reaction 5～10 hours in the presence of the catalyzer of catalytic amount, in the time of reaction, tell the water that reaction generates, collect then and obtain intermediate II;
Said catalyzer is selected from mineral acid or organic acid, and described mineral acid is sulfuric acid or phosphoric acid, and described organic acid is Phenylsulfonic acid or tosic acid;
Intermediate compound I and alcoholic acid mol ratio are:
Intermediate compound I: ethanol=1: 18～20.
7. method according to claim 6 is characterized in that, said catalyzer is sulfuric acid or phosphoric acid, Phenylsulfonic acid or tosic acid.
8. method according to claim 1, it is characterized in that wherein, step (3) comprises the steps: intermediate II that step (2) is obtained, reacted 4～8 hours down at 20～30 ℃, from reaction product, collect target product (S)-oxiracetam then with ammoniacal liquor;
In the ammonia in the ammoniacal liquor, intermediate II: the mol ratio of ammonia is:
Intermediate II: ammonia=1: 12～15;
The weight concentration of described ammoniacal liquor is 25～28%.
9. method according to claim 8 is characterized in that, collects the method for target product (S)-oxiracetam in the said reaction product, comprises the steps:
Reaction product is handled through strong acid cation exchange resin column, with the strongly basic anion exchange resin neutralization, filtered then, collect filtrate, reconcentration adds alcohol crystal then, obtains product (S)-oxiracetam.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4173569A (en) * | 1977-02-11 | 1979-11-06 | I.S.F. Spa | Preparation of pyrrolidine and pyrrolidin-2-one derivatives |
| CN1513836A (en) * | 2002-06-22 | 2004-07-21 | 张家港浩波化学品有限公司 | Method of preparing 4-hydroxy pyrrolidone-2-acetamine |
| CN1948285A (en) * | 2006-10-31 | 2007-04-18 | 张家港浩波化学品有限公司 | Method of preparing 4-hydroxy pyrrolidone-2-acetylamine |
| CN1956953A (en) * | 2004-05-25 | 2007-05-02 | 安国药品株式会社 | Process for the preparation of optically pure 4-hydroxy-2-oxo-1-pyrrolidine acetamide |
-
2009
- 2009-04-28 CN CN2009100501165A patent/CN101575309B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4173569A (en) * | 1977-02-11 | 1979-11-06 | I.S.F. Spa | Preparation of pyrrolidine and pyrrolidin-2-one derivatives |
| CN1513836A (en) * | 2002-06-22 | 2004-07-21 | 张家港浩波化学品有限公司 | Method of preparing 4-hydroxy pyrrolidone-2-acetamine |
| CN1956953A (en) * | 2004-05-25 | 2007-05-02 | 安国药品株式会社 | Process for the preparation of optically pure 4-hydroxy-2-oxo-1-pyrrolidine acetamide |
| CN1948285A (en) * | 2006-10-31 | 2007-04-18 | 张家港浩波化学品有限公司 | Method of preparing 4-hydroxy pyrrolidone-2-acetylamine |
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